DESCRIPTION: (Applicant's Description) The emerging field of molecular epidemiology offers new possibilities for identifying risk factors for breast cancer by taking into account individual susceptibility to carcinogenesis. As an adjunct to our on-going population-based case-control study of modifiable risk factors for breast cancer (R01 CA47147), we propose to evaluate polymorphisms in N-acetyl transferase 2 (NAT2) to study potential gene/environment interactions in breast cancer etiology. Such an approach may reveal important associations between smoking and breast cancer which have not been apparent using conventional epidemiologic methods. The hypotheses to be tested in this study are: 1) Risk of breast cancer varies according to NAT2 genotype; and 2) A deleterious effect of cigarette smoking on breast cancer patients will be detectable among "slow acetylators" who are long-term, heavy cigarette smokers as compared to nonsmokers with this genotype. Buccal smears will be obtained from a sequential sample of 400 recently diagnosed and interviewed patients and 400 controls. Over 85 percent of the eligible subjects in the on-going study have provided extensive information on known and suspected risk factors for breast cancer, including a complete history of active and passive smoking. In pilot studies, DNA has been successfully recovered from study subjects. Smear material not used for this analysis will be archived for the future study. This reserved DNA will be an important resource for testing emerging hypotheses of gene/environment interactions in breast carcinogenesis.